As the causative agent of the most severe form of the malaria in humans, Plasmodium falciparum is the source of significant global morbidity and mortality. In addition malaria imposes significant economic and social burdens on society. Though the malaria was eliminated from Europe and North America this century, mortality is probably now increasing, especially in sub-Saharan Africa (Greenwood and Mutabingwa, Nature 415:670-672, 2002). Part of this increase can likely be attributed to the spread of parasites that are resistant to inexpensive chemotherapies such as chloroquine. While the production of an effective vaccine would reduce the need for chemotherapy, attempts to produce protective immunity have met with little success as protection is short-lived (Richie and Saul, Nature 415:694-701, 2002). In both cases, genetic variation in the parasite population is an issue-because drug resistance is spread by variant alleles of drug pumps or drug targets and because the establishment of variation allows the parasite to evade the host's immune system. Because of the importance of genetic variation to the pathogenesis of P. falciparum new methods are needed to quickly discover variation in the parasite. In other species oligonucleotide-array-based hybridization methods allow allelic variation to be identified and scored, inexpensively and quickly, and on a genome-wide scale. An oligonucleotide array that contains 367226 different 25mer probes derived from the P. falciparum genome sequence is now available. By hybridizing genomic DNA to this array, in theory up to one-third of the variation in the 26 Mb genome could be detected as well as scored in genetic crosses. It is thus worthwhile to develop methods for using this array to identify allelic variation on genome-wide scale in P. falciparum. The exploratory work described herein should also be useful in determining whether hybridization-based methods could be used to identify particular isolates of other microbial pathogens, including those that may be used in bioterrorism. [unreadable] [unreadable]